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- Title
SNARE protein redistribution and synaptic failure in a transgenic mouse model of Parkinson's disease.
- Authors
Garcia-Reitböck P; Anichtchik O; Bellucci A; Iovino M; Ballini C; Fineberg E; Ghetti B; Della Corte L; Spano P; Tofaris GK; Goedert M; Spillantini MG; Garcia-Reitböck, Pablo; Anichtchik, Oleg; Bellucci, Arianna; Iovino, Mariangela; Ballini, Chiara; Fineberg, Elena; Ghetti, Bernardino; Della Corte, Laura
- Abstract
The pre-synaptic protein alpha-synuclein is the main component of Lewy bodies and Lewy neurites, the defining neuropathological characteristics of Parkinson's disease and dementia with Lewy bodies. Mutations in the alpha-synuclein gene cause familial forms of Parkinson's disease and dementia with Lewy bodies. We previously described a transgenic mouse line expressing truncated human alpha-synuclein(1-120) that develops alpha-synuclein aggregates, striatal dopamine deficiency and reduced locomotion, similar to Parkinson's disease. We now show that in the striatum of these mice, as in Parkinson's disease, synaptic accumulation of alpha-synuclein is accompanied by an age-dependent redistribution of the synaptic SNARE proteins SNAP-25, syntaxin-1 and synaptobrevin-2, as well as by an age-dependent reduction in dopamine release. Furthermore, the release of FM1-43 dye from PC12 cells expressing either human full-length alpha-synuclein(1-140) or truncated alpha-synuclein(1-120) was reduced. These findings reveal a novel gain of toxic function of alpha-synuclein at the synapse, which may be an early event in the pathogenesis of Parkinson's disease.
- Publication
Brain: A Journal of Neurology, 2010, Vol 133, Issue 7, p2032
- ISSN
0006-8950
- Publication type
journal article
- DOI
10.1093/brain/awq132